title: Prostaglandin D2 induces heme oxygenase-1 mRNA expression through the DP2 receptor.
abstract: Prostaglandin (PG) D(2) exerts multiple actions through interaction with distinct receptors, DP1 and DP2. We have shown that PGD(2) induces the expression of heme oxygenase-1 (HO-1) in the retinal pigment epithelium (RPE) that is essential for survival of photoreceptors. HO-1 is a key enzyme in physiological heme degradation. Here, we explored the mechanism for the PGD(2)-mediated induction of HO-1 expression using ARPE-19 human RPE cells. ARPE-19 cells secrete PGD(2) and express DP2 mRNA, but not DP1 mRNA. Treatment with a DP2 agonist, 15(R)-15-methyl-PGD(2) or DK-PGD(2), increased HO-1 mRNA expression, and pretreatment with a DP2 antagonist, CAY10471, decreased the magnitude of the PGD(2)-mediated HO-1 induction. By contrast, either DP1 agonist or antagonist caused only marginal influence on HO-1 expression. Moreover, transient expression assays showed the DP2 agonist activated the HO-1-gene promoter in the enhancer-dependent manner. Thus, PGD(2) induces HO-1 mRNA expression through DP2 receptor, linking the PGD(2)-DP2 signaling with heme homeostasis.
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: Soisungwan
authors.initials: S
authors.lastname: Satarug
authors.forename: Raewadee
authors.initials: R
authors.lastname: Wisedpanichkij
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Moore
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
mesh_terms: D002104:Cadmium / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006706:Homeostasis; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000201:enzymology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C533609:CAY 10471; D002227:Carbazoles; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D002104:Cadmium; D006418:Heme; D051547:Heme Oxygenase-1; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor